Impact of particles on the Planck HFI detectors: Ground-based measurements and physical interpretation

The Planck High Frequency Instrument (HFI) surveyed the sky continuously from August 2009 to January 2012. Its noise and sensitivity performance were excellent, but the rate of cosmic ray impacts on the HFI detectors was unexpectedly high. Furthermore, collisions of cosmic rays with the focal plane produced transient signals in the data (glitches) with a wide range of characteristics. A study of cosmic ray impacts on the HFI detector modules has been undertaken to categorize and characterize the glitches, to correct the HFI time-ordered data, and understand the residual effects on Planck maps and data products. This paper presents an evaluation of the physical origins of glitches observed by the HFI detectors. In order to better understand the glitches observed by HFI in flight, several ground-based experiments were conducted with flight-spare HFI bolometer modules. The experiments were conducted between 2010 and 2013 with HFI test bolometers in different configurations using varying particles and impact energies. The bolometer modules were exposed to 23 MeV protons from the Orsay IPN TANDEM accelerator, and to $^{241}$Am and $^{244}$Cm $\alpha$-particle and $^{55}$Fe radioactive X-ray sources. The calibration data from the HFI ground-based preflight tests were used to further characterize the glitches and compare glitch rates with statistical expectations under laboratory conditions. Test results provide strong evidence that the dominant family of glitches observed in flight are due to cosmic ray absorption by the silicon die substrate on which the HFI detectors reside. Glitch energy is propagated to the thermistor by ballistic phonons, while there is also a thermal diffusion contribution. The implications of these results for future satellite missions, especially those in the far-infrared to sub-millimetre and millimetre regions of the electromagnetic spectrum, are discussed.Comment: 11 pages, 13 figure

Modelling Service Level Agreements for Business Process Outsourcing Services

Many proposals to model service level agreements (SLAs) have been elaborated in order to automate different stages of the service lifecycle such as monitoring, implementation or deployment. All of them have been designed for computational services and are not well–suited for other types of services such as business process outsourcing (BPO) services. However, BPO services suported by process–aware information systems could also benefit from modelling SLAs in tasks such as performance monitoring, human resource assignment or process configuration. In this paper, we identify the requirements for modelling such SLAs and detail how they can be faced by combining techniques used to model computational SLAs, business processes, and process performance indicators. Furthermore, our approach has been validated through the modelling of several real BPO SLAsMinisterio de Economía y Competitividad TIN2012-32273Junta de Andalucía TIC-5906Junta de Andalucía P12-TIC-186

Using isotope dilution assays to understand speciation changes in Cd, Zn, Pb and Fe in a soil model system under simulated flooding conditions

Flooded soils are systems with complex chemistry and understanding the mechanisms that control the mobility and bioavailability of metals in these soils is important for their management. This work uses stable metal multi-element isotopic dilution combined with sequential extraction assays to help understand the changes in solid and solution speciation of Cd, Fe, Pb and Zn in a contaminated soil following submergence. However, it is necessary to ensure that the isotopic dilution principles, originally developed for aerobic soils, are not compromised; in particular due to the presence of non-labile colloids in the solution phase. In particular, no studies examining the validity of these assays in systems where rapid pH and Eh changes are occurring due to fermentation reactions have been published. Thus sucrose (0.42% and 1.26% added C) was used as a carbon source to stimulate bacterial mediated fermentation reactions allowing changes in Cd, Zn, Fe and Pb isotopic exchangeability, speciation and solution chemistry to be examined after 10, 20 and 42 days of submergence. Without the addition of added C, submergence for 42 days only produced minor changes in the speciation of the metals in solid or solution phases. However, the presence of easily labile carbon produced significant responses depending on the quantity of C added. Assessments of whether fermentation products caused over-estimation of the isotopically exchangeable pool of metals (E-values) were made by measuring concentrations with and without a resin purification step. Results showed generally good agreement over a pH range of 4–7 for Pb, Cd, Zn and Fe and demonstrate that fermentation by-products do not induce the formation of non-exchangeable metal colloids. E-value concentrations were compared with fractions extracted using a modified Tessier sequential extraction. With no carbonate phases present in the soils, the E-values for Cd, Zn, Fe and Pb compared favourably with the concentrations of metal present in the combined solution, exchangeable and specifically adsorbed fractions. This provided additional evidence that the conditions for the isotopic dilution assays were not violated as these fractions should be isotopically exchangeable. Combining results from the different treatments and stages of the reduction process, strong pH dependence was found for the isotopically exchangeable and the solution pools of Cd, Zn and Pb

PARE0009 COMMUNITY ADVISORY BOARD INPUT CAN MAKE LAY SUMMARIES OF CLINICAL TRIAL RESULTS MORE UNDERSTANDABLE

Background:Under European Union (EU) Clinical Trial regulations,1clinical research sponsors (CRSs) must ensure all studies performed in the EU are accompanied by a trial summary for laypersons, published within 1 year of study completion. These lay summaries should disseminate clinical trial results in an easy-to-understand way for trial participants, patient and caregiver communities, and the general public. The European Patients Forum (EPF)2and European Patients' Academy on Therapeutic Innovation (EUPATI)3encourage CRSs to engage with patient organisations (POs) in the development of lay summaries. This recognises the patients' contribution to clinical research and supports the development of patient-focused material.Objectives:We share learnings from a collaboration between scleroderma POs and a CRS to create the SENSCIS® trial (NCT02597933) written and video lay summaries.Methods:A community advisory board (CAB), comprising representatives from 11 scleroderma POs covering a range of countries/regions, was formed based on the EURORDIS charter for collaboration in clinical research.4Through three structured meetings, over a seven-month period, the CAB provided advice on lay summary materials (written and video) drafted by the CRS' Lay Summary Group (Fig. 1). At each review cycle, the CAB advice was addressed to make content more understandable and more relevant for patients and the general public.Results:The CAB advised that the existence of lay summaries is not well known in the patient community and also recommended the development of trial-specific lay summary videos to further improve understandability of the clinical trial results for the general public. Videos are a key channel of communication, enabling access to information for people with specific health needs and lower literacy levels. Following CAB advice, the CRS developed a stand-alone video entitled"What are lay summaries?"and a trial-specific lay summary video. Revisions to lay summary content (written and video) included colour schemes, iconography and language changes to make content more understandable. For videos, adjustments to animation speed, script and voiceover were implemented to improve clarity and flow of information (Fig. 2). Approved final versions of lay summary materials are publicly available on the CRS website. Translation into languages representing trial-site countries is in progress to widen access to non-English speakers and, where possible, local versions are being reviewed by the patient community.Conclusion:Structured collection and implementation of CAB advice can make lay summary materials more understandable for the patient community and wider general public.References:[1]EU. Summaries of clinical trial results for laypersons. 2018[2]EPF. EPF position: clinical trial results – communication of the lay summary. 2015[3]EUPATI. Guidance for patient involvement in ethical review of clinical trials. 2018[4]EURORDIS. Charter for Collaboration in Clinical Research in Rare Diseases. 2009Disclosure of Interests:Joep Welling Speakers bureau: Four times as a patient advocate for employees of BII and BI MIDI with a fixed amount of € 150,00 per occasion., Annelise Roennow: None declared, Maureen Sauvé Grant/research support from: Educational grants from Boehringer Ingelheim and Janssen., EDITH BROWN: None declared, Ilaria Galetti: None declared, Alex Gonzalez Consultant of: Payment made to the patient organisation (Scleroderma Research Foundation) for participation in advisory boards, Alexandra Paula Portales Guiraud: None declared, Ann Kennedy Grant/research support from: AS FESCA aisbl, Catarina Leite: None declared, Robert J. Riggs: None declared, Alison Zheng Grant/research support from: We get grants from Lorem Vascular; BI China,; Jianke Pharmaceutical Co., Ltd.; Kangjing Biological Co., Ltd.; COFCO Coca-Cola to organize national scleroderma meetings, offer patients service, holding academic meetings and other public activities, there is also a small part of the grants used to pay the workers in our organization., Consultant of: I worked as a paid consultant for BI. Pay-per-job., Speakers bureau: I was invited once to be a speaker at BI China's internal meeting and they paid me., Matea Perkovic Popovic: None declared, Annie Gilbert Consultant of: I have worked as a paid consultant with BI International for over 3 years, since Sept 2016., Lizette Moros Employee of: Lizette Moros is an employee of Boehringer Ingelheim, Kamila Sroka-Saidi Employee of: Paid employee of Boehringer Ingelheim., Thomas Schindler Employee of: Employee of Boehringer Ingelheim Pharma, Henrik Finnern Employee of: Paid employee of Boehringer Ingelheim

The global dimension in education and education for global citizenship: genealogy and critique

Encouraged by transnational organisations, curriculum policy-makers in the UK have called for curricula in schools and higher education to include a global dimension and education for global citizenship that will prepare students for life in a global society and work in a global economy. We argue that this call is rhetorically operating as a ‘nodal point’ in policy discourse a floating signifier that different discourses attempt to cover with meaning. This rhetoric attempts to bring three educational traditions together: environmental education, development education and citizenship education. We explore this new point of arrival and departure and some of the consequences and critiques

Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Protection of Visual Functions by Human Neural Progenitors in a Rat Model of Retinal Disease

BACKGROUND: A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. METHODOLOGY/PRINCIPAL FINDINGS: Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90–100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. CONCLUSIONS/SIGNIFICANCE: Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in vivo

Time-dependent integrity during storage of natural surface water samples for the trace analysis of pharmaceutical products, feminizing hormones and pesticides

Monitoring and analysis of trace contaminants such as pharmaceuticals and pesticides require the preservation of the samples before they can be quantified using the appropriate analytical methods. Our objective is to determine the sample shelf life to insure proper quantification of ultratrace contaminants. To this end, we tested the stability of a variety of pharmaceutical products including caffeine, natural steroids, and selected pesticides under refrigerated storage conditions. The analysis was performed using multi-residue methods using an on-line solid-phase extraction combined with liquid chromatography tandem mass spectrometry (SPE-LC-MS/MS) in the selected reaction monitoring mode. After 21 days of storage, no significant difference in the recoveries was observed compared to day 0 for pharmaceutical products, while for pesticides, significant losses occurred for DIA and simazine after 10 days (14% and 17% reduction respectively) and a statistically significant decrease in the recovery was noted for cyanazine (78% disappearance). However, the estrogen and progestogen steroids were unstable during storage. The disappearance rates obtained after 21 days of storage vary from 63 to 72% for the feminizing hormones. Overall, pharmaceuticals and pesticides seem to be stable for refrigerated storage for up to about 10 days (except cyanazine) and steroidal hormones can be quite sensitive to degradation and should not be stored for more than a few days